|Meta-analysis of the performance of 18F-FDG PET in cutaneous melanoma
|Jimenez-Requena F, Delgado-Bolton RC, Fernandez-Perez C, Gambhir SS, Schwimmer J, Perez-Vazquez JM, Carreras-Delgado JL
The review found that 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) diagnosis during staging and re-staging of cutaneous melanoma could be useful for the detection of distant metastases, but not for regional metastases. Given the limitations and variation between studies, and potential biases in the review process, the authors' conclusions should be treated with caution.
To evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in staging and re-staging of cutaneous melanoma.
MEDLINE, CANCERLIT and EMBASE were searched for studies published between January 2000 and January 2006; search terms were reported for the MEDLINE search in a supplementary online table. Studies were also identified from a previous meta-analysis (see Other Publications of Related Interest), whose search was from 1980 to 1999. The search was restricted to studies published in English. Attempts were made to find additional studies by reviewing the reference lists of retrieved articles.
Eligible studies had to assess 18F-FDG PET in 12 or more patients with cutaneous melanoma for detection of malignant lesions, both regional and distant metastases. Studies that did not report primary data sufficient to allow calculation of both sensitivity and specificity for detection of the lesions were eligible for inclusion for the assessment of quality, but were not eligible for inclusion in quantitative analyses. Studies that included patients with both non-cutaneous and cutaneous melanoma were excluded if data were not available for separate analyses of patients with cutaneous melanoma. Abstracts were excluded.
Characteristics of the included studies were reported only for studies published in the latest search between 2000 and 2006. The clinical use of 18F-FDG PET was for regional staging or for detection of distant metastases; in a few studies both outcomes were measured. The mean age of participants ranged from 47 to 61 years and the proportion of males to females ranged from 41 to 74% (where stated). For the detection of regional metastases, the reference test for most studies was sentinel node biopsy; for the detection of distant metastases, the reference tests included clinical follow-up or histopathology.
Two reviewers independently performed the study selection, with disagreements resolved by discussion or referral to a third reviewer.
Assessment of study quality
Study quality was assessed using the following seven criteria: description of study design, description of study population, indications leading to 18F-FDG PET use, technical and image interpretation issues, final confirmation, sensitivity and specificity data, and change in management information. Adherence to each question within the seven quality domains was considered adequate (A), partial (P), not addressed (N) or not applicable (N/A). A study was considered of high quality with A scores over 70%, of acceptable quality with A scores ranging from 50 to 70%, and of low quality with A scores lower than 50%. Quality scores for studies published prior to 2000 were obtained from the published data in the previous meta-analysis.
Two reviewers independently assessed the studies for validity, with disagreements resolved by discussion.
Data were extracted on the rates of true positive (positive 18F-FDG PET finding subsequently confirmed), false positive (positive 18F-FDG PET finding not confirmed), true negative (negative 18F-FDG PET finding subsequently confirmed as absence of malignant lesions), and false negative (negative 18F-FDG PET finding where malignant lesions were identified subsequently). These data were used to calculate the sensitivity, specificity, accuracy, positive likelihood ratio and negative likelihood ratio for each study and included in tables. Data were also extracted on the reference tests used for confirmation of 18F-FDG PET findings.
Data extraction was performed by one reviewer.
Methods of synthesis
Estimates of sensitivity and specificity from the included studies were combined to construct a summary receiver operating curve (ROC). Summary positive and negative likelihood ratios and diagnostic odds ratios (DORs), with 95% confidence intervals (CIs), were calculated with the DerSimonian Laird random-effects model. Homogeneity of the likelihood ratio and diagnostic odds ratio was compared with the Cochran's Q test, weighted by the inverse of the variances; summary effects were only reported where the global homogeneity test did not find significant differences. Meta-regression was undertaken to assess sources of heterogeneity.
Subgroup analysis was performed according to whether 18F-FDG PET was used for regional staging or detection of distant metastases. There was further subgrouping according to the method of counting findings: patients, lesions, basins, lymph nodes, areas, and scans.
Results of the review
Thirty studies were included in the review. Six of these studies were excluded from the quantitative analysis because data were not available for calculation of sensitivity or specificity, or because they were outdated by more recent publications. For the quantitative analyses, 486 patients were included in the analysis of diagnostic accuracy for regional staging and 737 patients were included for detection of distant metastases.
Quality of studies: Nine studies were considered high quality, twelve studies were considered acceptable quality, and nine studies were considered poor quality. All the studies from the later search used blinding and appropriate reference tests (histopathologic confirmation or clinical follow-up). Most studies had a follow-up of at least 12 months.
Diagnostic accuracy (based on a total of 24 studies): In the detection of regional metastases, there was global homogeneity for specificity (0.99, 95% CI 0.97 to 0.99; four studies) in the analysis of lymph nodes. None of the other analyses were homogeneous. In the detection of distant metastases, there was homogeneity for the negative likelihood (0.15, 95% CI 0.10 to 0.22; six studies) in the analysis of lesions. For the analyses of scans, there was global homogeneity for specificity (0.86, 95% CI 0.77 to 0.92; three studies), positive likelihood (5.86, 95% CI 3.64 to 9.43; three studies) and diagnostic odds ratio (37.89, 95% CI 15.8 to 90.86; three studies). None of the other analyses was homogeneous.
Meta-regression indicated that the year of publication was the factor that could best explain the heterogeneity between studies and had the greatest influence on the diagnostic odds ratio.
18FDG-PET was not useful for the evaluation of regional metastases, but could be useful for the detection of distant metastases in patients with cutaneous melanoma.
The review addressed a clear research question and inclusion criteria appeared appropriate. Three databases were searched and attempts were made to find other relevant studies by searching reference lists. Studies were selected for the review based on two separate searches, 1980 to 1999 and 2000 to 2006; it was not clear whether similar criteria were used for both searches. Searching was restricted to studies published in English, so language bias could not be excluded. Abstracts were excluded and no overt attempts were made to find unpublished studies, so publication bias could not be excluded. Data extraction was performed by one reviewer, so reviewer error and bias in this process could not be ruled out. Appropriate methods were used for the selection of studies and assessment of validity.
Study quality was appropriately assessed and analyses performed to determine whether quality was predictive of heterogeneity between studies. Substantial heterogeneity beween studies in many of the analyses meant that summary estimates were not helpful or robust; the populations, reference tests and follow-up times varied, and most studies were classified as weak evidence.
Given the limitations and variation between studies, and potential biases in the review process, the authors' conclusions should be treated with caution.
Implications of the review for practice and research
Practice: The authors stated that it may be beneficial to use 18F-FDG PET at an early stage in the management process in patients with cutaneous melanoma when metastases are suspected.
Research: The authors stated that more methodologically rigorous studies were required to assess the role of 18F-FDG PET in patients with cutaneous melanoma. These studies should include comparisons of 18F-FDG PET with other diagnostic tests and cost effectiveness analyses.
Jimenez-Requena F, Delgado-Bolton RC, Fernandez-Perez C, Gambhir SS, Schwimmer J, Perez-Vazquez JM, Carreras-Delgado JL. Meta-analysis of the performance of 18F-FDG PET in cutaneous melanoma. European Journal of Nuclear Medicine and Molecular Imaging 2010; 37(2): 284-300
Other publications of related interest
Schwimmer J, Essner R, Patel A, Jahan SA, Shepherd JE, Park K, Phelps ME, Czernin J, Gambhir SS. A review of the literature for whole-body FDG PET in the management of patients with melanoma. Quarterly Journal of Nuclear Medicine 2000;44(2):153-167.
Subject indexing assigned by NLM
Fluorodeoxyglucose F18 /diagnostic use; Humans; Incidence; Melanoma /epidemiology /radionuclide imaging; Positron-Emission Tomography /utilization; Radiopharmaceuticals /diagnostic use; Reproducibility of Results; Sensitivity and Specificity; Skin Neoplasms /epidemiology /radionuclide imaging
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.